PREDICT-GTN 1: Can we improve the FIGO scoring system in gestational trophoblastic neoplasia?

Gestational trophoblastic neoplasia (GTN) patients are treated according to the eight-variable International Federation of Gynaecology and Obstetrics (FIGO) scoring system, that aims to predict first-line single-agent chemotherapy resistance. FIGO is imperfect with one-third of low-risk patients developing disease resistance to first-line single-agent chemotherapy. We aimed to generate simplified models that improve upon FIGO. Logistic regression (LR) and multilayer perceptron (MLP) modelling (n = 4191) generated six models (M1-6). M1, all eight FIGO variables (scored data); M2, all eight FIGO variables (scored and raw data); M3, nonimaging variables (scored data); M4, nonimaging variables (scored and raw data); M5, imaging variables (scored data); and M6, pretreatment hCG (raw data) + imaging variables (scored data). Performance was compared to FIGO using true and false positive rates, positive and negative predictive values, diagnostic odds ratio, receiver operating characteristic (ROC) curves, Bland-Altman calibration plots, decision curve analysis and contingency tables. M1-6 were calibrated and outperformed FIGO on true positive rate and positive predictive value. Using LR and MLP, M1, M2 and M4 generated small improvements to the ROC curve and decision curve analysis. M3, M5 and M6 matched FIGO or performed less well. Compared to FIGO, most (excluding LR M4 and MLP M5) had significant discordance in patient classification (McNemar's test P < .05); 55-112 undertreated, 46-206 overtreated. Statistical modelling yielded only small gains over FIGO performance, arising through recategorisation of treatment-resistant patients, with a significant proportion of under/overtreatment as the available data have been used a priori to allocate primary chemotherapy. Streamlining FIGO should now be the focus.     

Predicting Survival for Chimeric Antigen Receptor T-Cell Therapy: A Validation of Survival Models Using Follow-Up Data From ZUMA-1

ObjectivesSurvival extrapolation for chimeric antigen receptor T-cell therapies is challenging, owing to their unique mechanistic properties that translate to complex hazard functions. Axicabtagene ciloleucel is indicated for the treatment of relapse or refractory diffuse large B-cell lymphoma after 2 or more lines of therapy based on the ZUMA-1 trial. Four data snapshots are available, with minimum follow-up of 12, 24, 36, and 48 months. This analysis explores how survival extrapolations for axicabtagene ciloleucel using ZUMA-1 data can be validated and compared.MethodsThree different parametric modeling approaches were applied: standard parametric, spline-based, and cure-based models. Models were compared using a range of metrics, across the 4 data snapshot, including visual fit, plausibility of long-term estimates, statistical goodness of fit, inspection of hazard plots, point-estimate accuracy, and conditional survival estimates.ResultsStandard and spline-based parametric extrapolations were generally incapable of fitting the ZUMA-1 data well. Cure-based models provided the best fit based on the earliest data snapshot, with extrapolations remaining consistent as data matured. At 48 months, the maximum survival overestimate was 8.3% (Gompertz mixture-cure model) versus the maximum underestimate of 33.5% (Weibull standard parametric model).ConclusionsWhere a plateau in the survival curve is clinically plausible, cure-based models may be helpful in making accurate predictions based on immature data. The ability to reliably extrapolate from maturing data may reduce delays in patient access to potentially lifesaving treatments. Additional research is required to understand how models compare in broader contexts, including different treatments and therapeutic areas.     

Associations between adolescents’ experience of general practitioners and health outcomes in England: a cross-sectional study of national data

BackgroundAdolescence is a key stage of the life course when lifelong health behaviours and attitudes to health care can be established. Poor experience of consultations with a general practitioner (GP) is common among adolescents, but little is known about whether poor experience in this group is associated with worse health status or outcomes. This study aimed to investigate this association with data from the 2014 Health Behaviour in School-Aged Children (HBSC) survey (England).MethodsWe used logistic regression to analyse data for 5335 participants aged 10–17 years in the HBSC survey. Four aspects of recent GP experience were studied: feeling at ease, being treated with respect, quality of GP explanation, and feeling able to talk about personal matters. Five dichotomised measures of health status or outcome were used (ever self-harmed; fair or poor self-reported health; frequent [at least weekly] low mood, sleeping problems, or headaches). We adjusted for participants’ sex, age, ethnicity, and family affluence score. Of 5178 participants, 1187 (23%) had not visited their GP within the past year and were excluded from the analysis.FindingsOf 3991 adolescents, 3632 (91%) felt treated with respect, 2091 (52%) could talk about personal matters, 1600 (40%) were satisfied with explanations, and 1221 (31%) felt at ease. Participants who reported poor experience of GP care were more likely to have poor health outcomes than were those who reported a good experience. For example, adolescents who did not feel at ease with their GP were more likely to report self-harm (adjusted odds ratio [AOR] 2·65, 95% CI 1·69–4·15; fair or poor health 1·64, 1·28–2·10; low mood 1·51, 1·25–1·82) and sleeping problems (1·41, 1·19–1·66). All GP indicators were associated with self-harm (AOR range 1·64–2·70; quality of GP explanation p=0·006, all others p<0·001) and feeling low (1·46–2·11, all p<0·001). The association with GP experience was less consistent for the other three health outcomes.InterpretationThis cross-sectional, observational study demonstrates that young people who report worse health symptoms, typically also report a poor experience of care. Further research is needed to investigate whether GP experience influences health outcomes—suggesting that improving GP experience might improve health outcomes in this group—or whether poor health status leads to more negative perceptions of care.FundingNone.     

Efficacy of home-based physical activity interventions in patients with autoimmune rheumatic diseases: A systematic review and meta-analysis

IntroductionPhysical activity (PA) has been receiving increasing interest in recent years as an adjuvant therapy for autoimmune rheumatic disease (ARDs), but there is scarce information about the efficacy of home-based PA for patients with ARDs.ObjectiveTo perform a systematic review and meta-analysis on the efficacy of home-based physical activity (PA) interventions in improving health-related quality of life, functional capacity, pain, and disease activity in patients with ARDs.MethodsSearches were performed in PubMed, Web of Science, Scopus, Cochrane, CINAHL database and Sport Discus. Trials were considered eligible if they included a home-based physical activity intervention. The population included adults with autoimmune rheumatic diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus, idiopathic inflammatory myopathies, systemic sclerosis and ankylosing spondylitis), comparisons included non-physical activity control or centre-based interventions (i.e., interventions performed on a specialized exercise centre) and the outcomes were quality of life, pain, functional capacity, disease activity and inflammation.ResultsHome-based physical activity improved quality of life (p<0.01; g = 0.69; IC95%, 0.61 to 1.07) and functional capacity (p = 0.04; g = - 0.51; IC95%, -0.86; -0.16), and reduced disease activity (p = 0.03; g = - 0.60; IC95%, -1.16; -0.04) and pain (p = 0.01; g = -1.62; IC95%, -2.94 to -0.31) compared to the non-physical activity control condition. Additionally, home-based physical activity interventions were as effective as centre-based interventions for all investigated outcomes.ConclusionHome-based PA is an efficacious strategy to improve disease control and aleviate symptoms in ARD.